The biotransformation of gamma-aminobutyric acid (GABA) to succinic acid semialdehyde, which is catalyzed by the enzyme GABA-transaminase (GABA-T), is the primary reaction responsible for the catabolism of GABA, an inhibitory neurotransmitter of the central nervous system. It is known that low levels of endogenous GABA are associated with seizures disorders (such as those produced by epilepsy, alcohol withdrawal, or barbiturate withdrawal), with disorders involving involuntary movement (such as Huntington's chorea, the extrapyrimidal effect of drugs, for example tardive dyskinesia) and certain psychoses (such as schizophrenia and mania/depression). Blockade of the transformation of GABA to succinic acid semialdehyde, such as by irreversible inhibition of GABA-T, can elevate GABA levels in the central nervous system (CNS) and, thus provides a means for treating those disorders of the central nervous system associated with low GABA levels.
Certain compounds are known to be irreversible inhibitors of GABA-T and thereby elevate brain levels of GABA, for example fluorinated methyl gamma-aminobutyric acid and certain derivatives thereof (see U.K. Patent Specification No. 2005264A). Further, it is disclosed in U.K. Patent Specification No. 2058052A that fluorinated methyl aminopropionic acids and certain derivatives thereof are also irreversible inhibitors of GABA-T.